Diclofenac sodium topical solution with dimethyl sulfoxide, a viable alternative to oral nonsteroidal anti-inflammatories in osteoarthritis: review of current evidence

Figures & data

Table 1 Overview of randomized, double-blind clinical trials of diclofenac sodium topical solution

Reference	Interventions	Duration	Patientsa (n)	Description of patients	Primary efficacy variable(s)	Other efficacy variables
Bookman et al^Citation23	TDiclo Vehicle control Placebo control	4 weeks	248	Men and women (18–80 years) Primary, radiologically verified OA of the knee At least moderate pain	WOMAC pain	WOMAC physical function WOMAC stiffness score PGA WOMAC pain on walkingb
Roth and Shainhouse^Citation24	TDiclo Vehicle control	12 weeks	326	Men and women (40–85 years) Primary, radiologically verified OA of the knee Pain flare	WOMAC pain WOMAC physical function PGA	WOMAC stiffness WOMAC pain on walkingb
Baer et al^Citation25	TDiclo Vehicle control	6 weeks	216	Men and women (40–85 years) Primary, radiologically verified OA of the knee Pain flare	WOMAC pain WOMAC physical function PGA	WOMAC stiffness WOMAC pain on walkingb
Simon et al^Citation26	TDiclo Oral diclofenac TDiclo + oral diclofenac Vehicle control Placebo control	12 weeks	775	Men and women (40–85 years) Primary, radiologically verified OA of the knee Pain flare	WOMAC pain WOMAC physical function POHA	WOMAC stiffness PGA
Tugwell et al^Citation27	TDiclo Oral diclofenac	12 weeks	622	Men and women (40–85 years) Primary, radiologically verified OA of the knee At least mild symptoms of OA	WOMAC pain WOMAC physical function PGA	WOMAC stiffness WOMAC pain on walkingb Percent responders (OMERACT-OARSI criteria)

a Notes: Number of patients included in safety analysis;

b First question in the WOMAC pain subscale.

Abbreviations: DMSO, dimethyl sulfoxide; OA, osteoarthritis; WOMAC, Western Ontario and McMaster Universities; OMERACT, Outcome Measures in Arthritis Clinical Trials; OARSI, Osteoarthritis Research Society International; PGA, patient global assessment; POHA, patient overall health assessment; TDiclo, diclofenac sodium topical solution with DMSO.

Figure 1 Improvement from baseline to final assessment in WOMAC pain score with diclofenac sodium topical solution and vehicle control. Pain score was based on five questions scored on a scale of 0 to 4.

Notes: *P = 0.023; ^†P = 0.001; ^‡P = 0.003; ^§P = 0.009. P values are vs vehicle control.
Abbreviation: WOMAC, Western Ontario and McMaster Universities.

Figure 2 Improvement from baseline to final assessment in WOMAC physical function score with diclofenac sodium topical solution and vehicle control. Physical function score was based on 17 questions scored on a scale of 0 to 4.

Notes: *P = 0.002; ^†P = 0.001; ^‡P = 0.026. P values are vs vehicle control.
Abbreviation: WOMAC, Western Ontario and McMaster Universities.

Table 2 Patient perception of osteoarthritis symptoms and overall health status as assessed by the PGA or POHA, after treatment with diclofenac sodium topical solution, vehicle control, or placebo

Reference	Variable	TDiclo	Vehicle control	P valuea	Placebo control	P valueb
Bookman et al^Citation23	PGA (sum of scores at weeks 1, 2, 3, and 4)	6.7	7.8	0.039	7.8	0.025
Roth and Shainhouse^Citation24	PGA (change from baseline)	−1.3 (42.2%)	−0.9 (30.4%)	0.003	–	–
Baer et al^Citation25	PGA (change from baseline)	−1.3 (41.9%)	−0.7 (21.9%)	0.0001	–	–
Simon et al^Citation26	PGA (change from baseline)	−1.36 (43.6%)	−1.07 (34.2%)	0.018	−1.01 (33.2%)	0.016
	POHA (change from baseline)	−0.95 (40.6%)	−0.65 (28.3%)	0.016	−0.37 (16.7%)	<0.0001

a Notes: TDiclo vs vehicle control;

b TDiclo vs placebo. PGA and POHA were assessed on a scale of 0 to 4. Values shown indicate change from baseline (% improvement).

Abbreviations: OA, osteoarthritis; PGA, Patient Global Assessment; POHA, Patient Overall Health Assessment; TDiclo, diclofenac sodium topical solution.

Figure 3 Percent change from baseline to final assessment in efficacy variables with diclofenac sodium topical solution and oral diclofenac.

Notes: *P = 0.429; ^†P = 0.319; ^‡P = 0.956; ^§P = 0.439; ^¶P = 0.23; ^#P = 0.06; **P = 0.13. P values are vs oral diclofenac.
Abbreviations: PGA, Patient Global Assessment; POHA, Patient Overall Health Assessment.

Table 3 Adverse events in studies comparing diclofenac sodium topical solution with oral diclofenac^26,27

Adverse events (%)	Tugwell et al^Citation27		Simon et al^Citation26
	TDiclo	Oral diclofenac	TDiclo	Oral diclofenac
Application site
Dry skin	27	1a	18.2	2.6
Rash	12	2a	–	–
Paresthesia	0.6	0.6	–	–
Pruritus	6	0.6a	1.3	0.0
Urticaria	0.3	0.3	–	–
Vesiculobullous rash	5	0a	1.9	0.7
Contact dermatitis	–	–	2.6	0.7
Gastrointestinal
All GI events	35	48a	6.5	23.8
Abdominal pain	12	22a	3.2	7.3
Constipation	8	10	–	–
Diarrhea	9	17a	1.3	4.6
Dyspepsia	15	26a	2.6	4.0
Flatulence	10	17a	–	–
Melena	1	2	–	–
Nausea	8	13a	0.0	2.0
Vomiting	2	2	ND	ND
Laboratory parametersb
AST	2	10a	6.9	19.6
ALT	5	17a	4.1	18.8
Hemoglobin	2	10a	2.1	5.8
Creatinine	1	3	2.8	7.2

a Notes: P < 0.05 vs TDiclo with DMSO. No statistical analysis was performed in Simon et al;²⁶

b Percentage of patients changing from normal levels at baseline to abnormal levels during the study.

Abbreviations: GI, gastrointestinal; AST, aspartate aminotransferase; ALT, alanine aminotransferase; DMSO, dimethyl sulfoxide; TDiclo, diclofenac sodium topical solution.

Figure 4 Skin irritation scores in a long-term, open-label study of diclofenac sodium topical solution.³⁶

Notes: 0 = normal; 0.5 = dryness or flaking; 1 or 2 = erythema with or without induration; 3 or 4 = erythema with induration and vesicles or bullae.

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